Significant scientific advances in the fields of immunology and protein science are driving the development of biotherapeutic drugs in a growing range of therapeutic areas beyond oncology. These advances support the identification of new and unique targets,
new approaches to developing biotherapeutics for unserved medical needs, methods of binding to illusive targets and translational science for patient stratification and drug development for niche indications. The PEGS Emerging Indications for Therapeutic
Antibodies conference provides a forum for research organizations with diverse portfolios to explore new science and technology in the development of a next generation of safe and effective therapeutics in an important set of emerging indications.
Final Agenda
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SUNDAY, MAY 3
Recommended Short Course(s)*
SC2: Translational Biotherapeutic Development Strategies: Part I, Discovery, Molecular Assessment and Early Stage Development - Detailed Agenda
SC6: Translational Biotherapeutic Development Strategies: Part II, Analytical and Clinical Considerations - Detailed Agenda
*Separate registration required.
MONDAY, MAY 4
7:00 am Registration and Morning Coffee
8:30 Chairperson’s Opening Remarks
Sarav Rajan, PhD, Senior Scientist, AstraZeneca R&D
8:40 Development of a Novel Therapeutic Antibody Drug Conjugate for the Treatment of Autoimmune Disease
Michael McPherson, PhD, Senior Principal Research Scientist, Discovery Biologics, AbbVie
We have developed a plasma-stable antibody drug conjugate (ADC) that has glucocorticoid receptor modulator (GRM) molecules linked to an anti-TNF-α mAb. This ADC is targeted to TNF-α expressing inflammatory cells and internalized into
lysosomes where GRM payload is released. This significantly reduces the efficacious GRM dose to below levels that induce undesired side effects. Activity of a surrogate anti-TNF GRM conjugate in inflammatory disease models will be described.
9:10 Engineered Antibody Platforms for Receptor Agonism
Greg Lazar, PhD,
Director and Senior Scientist, Antibody Engineering, Genentech
The majority of immune agonist antibodies currently in clinical development rely on extrinsic crosslinking by Fc receptors to enable in vivo pharmacologic activity. We have explored multiple technology platforms
to enable antibodies to promote receptor signaling without relying on Fc receptor engagement. This talk will describe engineering approaches and considerations, present data demonstrating in vitro and
in vivo proof of concept, and discuss biological and clinical context for immunotherapy.
9:40 Complement Mediation as a Therapeutic Strategy in Autoimmune and Inflammatory Diseases
Claire
Harris, PhD, Professor, Molecular Immunology, Newcastle University, United Kingdom
The driving role of complement in a single disease, paroxysmal nocturnal hemoglobinuria, provoked the development and FDA approval in 2007 of eculizumab (Soliris™), an anti-C5 antibody. No other drug has since been approved for any other
indication. A high attrition rate in complement drug development means that the unmet need for therapy in many complement-driven diseases remains. I will discuss the challenges associated with therapeutic inhibition of complement, highlighting
lessons learnt and hurdles cleared by various different therapeutic approaches.
10:10 Networking Coffee Break
10:50 Dissecting Anti-Beta-Amyloid Clinical Outcomes; Why Do Some Antibodies Appear to Work while Others Don’t?
Charles
Glabe, PhD, Professor, Molecular Biology and Biochemistry, University of California, Irvine
Several active vaccines and monoclonal antibodies have been tested in human clinical trials and despite removing amyloid deposits, only Aducanumab has been reported to slow cognitive decline. Those that failed in clinical trials target plaques
that may represent tombstone markers of antecedent amyloid pathology. Antibodies that target oligomers, but do not bind plaques, have not been fully evaluated yet. Anti-amyloid antibodies with these and other novel properties remain to
be tested in human clinical trials.
11:20 Preclinical Characterization of a Brain Shuttle Anti-Amyloid Antibody
Jens Niewoehner, PhD, Senior Principal Scientist, Pharmaceutical Research and Early Development, Roche Innovation Center Munich, Germany
Brain uptake of therapeutic antibodies has been reported using different experimental systems and diverse methodologies, but the precise measurement of drug levels in all relevant brain compartments is often hampered by technical difficulties.
We present the comprehensive characterization of a Brain Shuttle anti-amyloid antibody in Cynomolgus monkeys, including modeling-supported plasma and brain pharmacokinetics.
11:50 KEYNOTE PRESENTATION: Challenges and Opportunities for Biotherapeutics Discovery and Development in Rare Diseases
Madhusudan Natarajan, PhD, Head, Rare Diseases DDU, Takeda
An ongoing biopharma investment in rare disease research, especially in monogenic disorders, coupled with recent advancements and success stories in genetic therapies have fueled a remarkable proliferation of biotherapeutic development at
this intersection of therapeutic area and modality. I will showcase examples of opportunities that this intersection provides to “traditional” protein and antibody biotherapeutic development, as well as the associated challenges
with these approaches.
12:20 pm Sponsored Presentation (Opportunity Available)
12:50 Session Break
12:55 Luncheon Presentation (Sponsorship Opportunity Available)
1:25 LUNCHEON PRESENTATION II: Talk Title to be Announced
Jacob Glanville, Founding Partner & CEO, Distributed Bio
1:55 Session Break
2:20 Problem-Solving Breakout Discussions - View All Breakout Discussion Topics
TABLE: Biotherapeutics for Respiratory Indications
Moderator: Bas van der Woning, PhD, Research Fellow, arGEN-X, Belgium
- What are the biggest unmet medical needs in respiratory diseases (asthma, cystic fibrosis, COPD, idiopathic pulmonary fibrosis, etc.)
- Systemic versus local administration of biotherapeutics
- Challenges of local administration of biotherapeutics
- Methods to measure an effect on lung function (spirometry, CT, 3He MRI, airway resistance, ect.)
- Biomarkers (eosinophils, neutrophils, IgE, FeNO, ..any new biomarkers?)
TABLE: Antibody Targeting and Delivery Strategies for CNS Indications
Moderator: Charles Glabe, PhD, Professor, Molecular Biology and Biochemistry, University of California, Irvine
- Do antibodies that modulate inflammation or complement activity have potential therapeutic activity in CNS diseases?
- Does immunotherapy hold promise for other amyloid related neurodegenerative diseases? If so, is it possible to have a broad spectrum or universal antibody for neurodegenerative diseases?
- What parameters are important for making immunotherapy more effective?
- Does amyloid structural polymorphism mean that immunotherapy needs to be personalized according to specific conformational strain?
TABLE: Strategies for Modulating, Targeting and Directing T Cell Activity for Therapeutic Gain
Moderator: Elissa Leonard, PhD, Postdoctoral Fellow, Biomedical Engineering, Johns Hopkins University
- What are the most viable emerging or established strategies for directing T cell specificity? Engineered TCRs? Expansion of endogenous populations? CARs?
- Other stimulatory signals that can direct lineage and suppressive/inflammatory activity
- Engineering or controlling persistence
- Therapeutic viability in terms of cost and scale
3:20 Networking Refreshment Break
4:00 Chairperson’s Remarks
K. Dane Wittrup, PhD, J.R. Mares Professor, Chemical Engineering & Bioengineering, Massachusetts Institute of Technology
4:10 From Energy to Machine Learning
George Church,
PhD, Professor of Genetics, Harvard Medical School; Professor of Health Sciences and Technology, Harvard and the Massachusetts Institute of Technology (MIT)
In 1974, I adapted energy optimization methods for use in models of nucleic acids, protein and their interactions, and then for use in crystallographic refinement. In the last days of the second millennium, David Baker's team won the Critical
Assessment of Structure Prediction (CASP) by an unbelievable margin. Since then, our labs exchanged 3 PhD students (Dantas, Raman, Lajoie), for Wannier from Mayo's group, Stranges from Kuhlman, and Mandell from Kortemme. We engineered
new sensor proteins for metabolic engineering, essential proteins with non-standard amino acids for biocontainment, and polymerase-pore fusions for nanopore sequencing. None of this prepared us for the revolution following Gleb Kuznetsov
joining our lab in 2012, joined soon by Surge Biswas, Pierce Ogden, Ethan Alley, and Sam Sinai. Together we abruptly moved to "sequence only" deep machine learning for protein design – ranging from fluorescent proteins to AAV
capsids to antibodies. When combined with libraries of millions of designed gene segments from chip-synthesis and rapid testing, each design cycle can take large leaps in sequence space and function space.
4:55 The Case for Intelligent Design in Protein Engineering
Jamie Spangler,
PhD, Assistant Professor, Biomedical Engineering and Chemical & Biomolecular Engineering, Johns Hopkins University
Directed evolution is in its prime, and it is deepening our understanding of biological systems and empowering therapeutic design. Recent breakthroughs in structural biology, computational design, and high-dimensional data analytics afford
us the unprecedented opportunity to apply molecular, structural, and computational principles to guide protein engineering, employing a so-called “intelligent design” approach. This talk will highlight how my lab harnesses
this interfacial approach to overcome the deficiencies of natural proteins.
5:40 Welcome Reception in the Exhibit Hall with Poster Viewing (Co-Sponsorship Opportunity Available)
7:15 End of Day
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TueSDAY, MAY 5
8:00 am Registration and Morning Coffee
8:25 Chairperson’s Remarks
JT Koerber, PhD, Senior Scientist, Antibody Engineering, Genentech
8:30 New Biotherapeutic Approaches for Targeting PCSK9
Robert Giugliano, MD, MSc, Professor, Medicine, Harvard Medical School
PCSK9 inhibitors represent the third proven class of medications (following statins and ezetimibe) to reduce LDL-cholesterol and prevent cardiovascular events. The first two PCSK9 inhibitors approved for clinical use were monoclonal antibodies,
but other approaches, including antisense oligonucleotides and small interfering RNAs, have been studied in humans. Mimetic peptides, LDL-receptor antagonists, small molecules, vaccines, and gene silencing approaches are in earlier
stages of development.
9:00 Structure-Guided Discovery of a Single-Domain Antibody Agonist against Human Apelin Receptor
Mei-Yun Zhang, PhD, Principal Scientist, Antibody Discovery, Amgen, China
Developing antibody agonists targeting G-protein-coupled receptors (GPCRs) remains a big challenge. Here we report the co-crystal structure of human apelin receptor (APJ) with a potent orthosteric single-domain antibody antagonist, JN241,
and the structure-guided conversion of JN241 into a full agonist, JN241-9, to human APJ. Modeling and molecular dynamics simulation shed light on JN241-9-stimulated receptor activation, providing structural insights for discovering
agonistic antibodies against class A GPCRs.
9:30 The Adipocyte as a Source for Novel Targets for Therapeutic Antibodies for Metabolism, Fibrosis and Cancer
Philipp Scherer, PhD, Professor and Director, Touchstone Diabetes Center, UT Southwestern
Adipose tissue dysfunction is at the heart of diabetes, fatty liver disease, organ fibrosis and enhanced growth for invading tumor lesions in a variety of cancers. We have targeted two key players in that area, leptin and endotrophin.
Neutralizing antibodies against these factors whose production is enriched in metabolically challenged adipose tissue are highly effective in preclinical settings as anti-obesity, anti-diabetic, anti-fibrotic, and chemosensitizing
agents in the breast cancer area.
10:00 Coffee Break in the Exhibit Hall with Poster Viewing
10:50 Rapid Capture and Screening of the Native Human Antibody Repertoire for the Discovery of Therapeutic Antibodies
Sarav
Rajan, PhD, Senior Scientist, AstraZeneca R&D
The human antibody repertoire is a valuable source of therapeutic grade antibodies. However, identifying the rare B cells expressing these antibodies can be challenging. We have built a platform that uses microfluidics to encapsulate millions
of primary B cells into droplets, capturing a paired repertoire that can be screened by phage-display. This presentation will describe the technology and its use in rapidly identifying natively-paired and functional antibodies across
multiple campaigns.
11:20 Antibody-Based Scaffolds to Activate T Cells Targeting CMV and EBV
Elissa Leonard, PhD, Postdoctoral Fellow, Biomedical Engineering, Johns Hopkins University
CMV and EBV are pervasive, typically asymptomatic viral infections that can be deadly for immunocompromised individuals. Patients suffering from these infections have been successfully treated with transfer of ex vivo expanded virus-specific T cells in clinical trials. This treatment is labor-intensive and highly individualized, limiting broader use. Combining an immunostimulatory IL-2/antibody fusion protein with viral antigens, we are developing
an injectable alternative for robust virus-specific T cell activation.
11:50 Engineering Antimicrobial Proteins: Co-Evolutionary Models Aid Molecular Discovery
Benjamin Hackel, Associate Professor, Chemical Engineering and Materials Science, University of Minnesota
Antimicrobial proteins (AMPs) present the opportunity for efficient discovery of potent, selective therapeutics for antibiotic-resistant infection. This presentation will discuss platforms to engineer AMP stability, selectivity, and potency
via bioinformatics-guided library design and high-throughput discovery assays. Co-evolutionary models enhanced library strategies to engineer endolysin stability and activity against Clostridium perfringens and Enterococcus. A sequence
depletion assay mapped oncocin’s sequence-function relationship. These methods are broadly applicable to protein engineering.
12:20 pm Session Break
12:25 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on your Own
1:25 Ice Cream Break in the Exhibit Hall with Poster Viewing and Poster Award
2:00 Chairperson’s Remarks
Elissa Leonard, PhD, Postdoctoral Fellow, Biomedical Engineering, Johns Hopkins University
2:05 Antibody Pliers: A Novel Antibody MOA for Asthma
JT
Koerber, PhD, Senior Scientist, Antibody Engineering, Genentech
The serine protease β-tryptase is an important mediator of the allergic inflammatory responses in asthma. Protease inhibitory antibodies employ a mechanism of action (MOA) in which Fab binding directly or allosterically inhibits the
protease. I will discuss a novel inhibitory anti-tryptase antibody with a unique bivalent IgG-driven MOA that reveals a new way in which IgGs can inhibit a target and may provide a new strategy for engineering novel antibodies.
2:35 Protein Crystallization Promotes Type 2 Immunity and Is Reversible by Antibody Treatment
Bas van der Woning, PhD, Research Fellow, arGEN-X, Belgium
Charcot-Leyden crystals (CLCs) consisting of galectin-10 (Gal10) protein are frequently observed in eosinophilic diseases, such as asthma. We found that CLCs stimulated innate and adaptive immunity and acted as a type-2 adjuvant. Antibodies
directed against key epitopes of the CLC crystallization interface dissolved CLCs from patient-derived mucus within hours and reversed crystal-driven inflammation, goblet-cell metaplasia, immunoglobulin E synthesis, and bronchial
hyperreactivity in a humanized mouse model of asthma.
3:05 Presentation to be Announced
3:35 Refreshment Break in the Exhibit Hall with Poster Viewing
4:25 The Development of Novel WNT Signal Modulating Platforms and their Initial Application to Study Functions of FZDs in Different Tissues
Yang Li, PhD, Vice President, Biology, Surrozen Inc.
WNT molecules have the potential to induce tissue regeneration and repair. However, their poor biophysical characteristics and lack of selectivity have hindered their application as therapeutics. We have developed a novel antibody
based platform for potent, selective WNT surrogate generation, and identified key requirements for maximal signaling.
4:55 Identification of Antibodies that Target the Blood-Brain Barrier
Eric
Shusta, PhD, Professor, Chemical and Biological Engineering, University of Wisconsin-Madison
The blood-brain barrier presents a major obstacle to brain drug delivery. We have developed several different enabling platforms for the identification of antibodies against blood-brain barrier resident receptors that could ultimately
be used to ferry drug cargo into the brain. Here we will describe our recent efforts to identify such blood-brain barrier-targeting antibodies.
5:25 End of Emerging Indications for Therapeutic Antibodies
5:30 Registration for Dinner Short Courses
6:00-8:30 pm Recommended Dinner Short Course*
SC11: Developability of Bispecific Antibodies: Assays and Case Studies
*Separate registration required.
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